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Mechanopriming and Stem Cells

Scientists continue to push the boundaries of what is or is not possible with stem cell therapy, broadening the number of people and categories of patients who will potentially benefit from this innovative therapy. One new breakthrough has been in terms of mechanopriming.

What Is Mechanopriming?

Mechanopriming is likely a term that most people outside the medical community have not heard. What is mechanopriming? Mechanopriming is a technique developed by innovators at MIT. This technique developed out of an understanding that patients recovering from treatment for blood cancers are often medically vulnerable, often developing a wide range of concerning infections? Why does this happen? Many blood cancers are treated by irradiating the patient’s bone marrow, effectively killing off the diseased cells. However, healthy cells are also impacted by this all-encompassing blanket radiation. And, after treatment, these cells, such as infection-fighting white blood cells, can be slow to recover. The bone marrow simply does not generate these blood cells at the same right.

Recognizing that the damaged bone marrow may not be able to regenerate these cells, mechanopriming allows the stem cells (specifically mesenchymal stem cells) to grow in an artificial, but healthy environment. This artificial environment has been carefully created so that its mechanical properties fully mimic what real bone marrow is like. The cells that grow on this surface are then able to differentiate into other types of cells, including: platelets and white and red blood cells.

Interestingly, the team of MIT scientists working on this project describe it as being very similar to growing plants, creating a soil that is conducive to cell growth. The only difference is that this soil is for human cells. The mesenchymal stem cells (MSCs) are the fertilizer that allows the other cells to differentiate and grow more, as needed.

All Stem Cells Are Not Created Equally

Often, people tend to lump all stem cells together … referring to them as the umbrella term, stem cells. However, stems cells are very different. For example, the vast majority of stem cell transplants use HPSCs. The MIT team, however, contends that including MSCs is more likely to result in successful outcomes. The MSCs are able to differentiate and produce different types of cells, and they also secrete proteins that can positively impact the environment for hematopoietic stem cells (HPSCs).

However, MSCs are not perfect. There are certain drawbacks associated with using them.

Although MSCs are capable of dividing and differentiating into a wide range of different cells, not all MSCs will do this. In fact, studies suggest that only approximately 20 percent of MSCs will divide and replicate in the desired manner. To address this limitation, the MIT team is looking at innovations that will allow scientists in the laboratory to differentiate between MSCs that will or will not replicate. And, then utilize these highly primed cells effectively.

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Why Are MSCs More Effective in Generating Outstanding Outcomes?

The MIT team carefully explored results from previous stem cell research and were able to determine that what made MSCs so effective in post-cancer recovery was that MSCs secrete osteopontin. Mice who are treated with or exposed to osteopontin have dramatically improved survival rates.

This was the first step in the mechanopriming process.

The next step was looking at the materials that were involved in the process.

Prior to the work of the innovative MIT team, stem cells were grown on simple plastic or glass sheets. But, MIT scientists recognized that the surface that was used to grow stem cells can affect how these stem cells multiply and differentiate. In other words, the medium matters. Because of this, the MIT team decided to utilize a complex polymer, PDMS.

They then began to think about how this PDMS could be changed to enhance growth and differentiation among the stem cells. Two factors that the MIT scientists looked at were stiffness and viscosity; and the team experimented with these factors, exploring which fabrications resulted in the best outcomes for the MSCs. Perhaps, not surprisingly, the MIT team discovered that the MSCs performed best on materials that most closely approximated a person’s real bone marrow. Therefore, research should continue into ways to produce a polymer that closely approximates stem cells.

What Did the Results Show?

Initial results appear to be very promising. The MIT team injected these mechanoprimed MSCs into mice, while also testing traditional MSC cultures on other mice. The recovery rate, and the speed at which recovery occurred, was dramatically better for the mechanoprimed MSCs. The rate was even better than for the mice who had been treated with MSCs that had been pre-sorted with an earlier technology.

Even though these mice studies are still early stage studies, the MIT team believes that these results will be able to be extended to humans. And, this new technology will likely be particularly impactful for patients who have blood cancers that have been treated with aggressive radiation therapy.

Moving forward, the MIT team will likely look at future innovations and ways to continue to push the envelope of stem cell therapy. There are two likely roads for this innovation. First, the MIT team is considering ways to combine both MSCs and HPSCs so that patients can receive the unique benefits offered by both types of stem cells. Second, the team, as well as other scientists around the world, will likely turn their attention to exploring how mechanoprimed cells can be used to address a wide range of other health conditions, such as rheumatoid arthritis and Parkinson’s Disease, among others.

The future of mechanopriming is fascinating and promising, and it may offer hopes for millions of Americans, as well as people from around the world, who are debilitated by post-treatment effects of cancer treatment.

In Conclusion

As technology continues to grow and evolve, stem cell therapy is pushing the envelopes of what is medically and scientifically possible. Treatments that were seen as impossible only decades ago are now feasible. And, this profoundly changes the course of disease treatment. One important breakthrough that was explained in detail above is mechanopriming. Mechanopriming combines best practice knowledge about stem cell therapy and the latest innovations in material research. Mechanopriming is based on the understanding that MSCs generally lead to better patient outcomes than what is seen with HPSCs, the cells that are traditionally used in transplant situations.

Unfortunately, there are drawbacks associated with MSCs, including the fact that not all MSCs grow and replicate. Only a small fraction of them do. Therefore, mechanopriming looks at ways to stimulate and grow the right kind of MSCs. The specially designed polymer at MIT, closely resembling actual bone marrow tissue in viscosity and other key factors, allowed this to happen. MSC cells that are capable of producing and secreting osteopontin grew and flourished in this environment. And, when these cells were injected into mice, the mice had better recovery rates than mice who had undergone traditional stem cell transplants.

It is important to remember that these results are still early stage. But, this does not change the fact that these results are highly promising and that they potentially offer opportunities and new hope to millions and millions of people.

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